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- EMDB-36670: Cryo-EM structure of the panda P2X7 receptor in complex with PPADS -
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Open data
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Basic information
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Title | Cryo-EM structure of the panda P2X7 receptor in complex with PPADS | |||||||||
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![]() | Channel / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() purinergic nucleotide receptor activity / extracellularly ATP-gated monoatomic cation channel activity / response to ATP / calcium ion transmembrane transport / postsynapse / ATP binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
![]() | Sheng D / Hattori M | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into the orthosteric inhibition of P2X receptors by non-ATP analog antagonists. Authors: Danqi Sheng / Chen-Xi Yue / Fei Jin / Yao Wang / Muneyoshi Ichikawa / Ye Yu / Chang-Run Guo / Motoyuki Hattori / ![]() Abstract: P2X receptors are extracellular ATP-gated ion channels that form homo- or heterotrimers and consist of seven subtypes. They are expressed in various tissues, including neuronal and nonneuronal cells, ...P2X receptors are extracellular ATP-gated ion channels that form homo- or heterotrimers and consist of seven subtypes. They are expressed in various tissues, including neuronal and nonneuronal cells, and play critical roles in physiological processes such as neurotransmission, inflammation, pain, and cancer. As a result, P2X receptors have attracted considerable interest as drug targets, and various competitive inhibitors have been developed. However, although several P2X receptor structures from different subtypes have been reported, the limited structural information of P2X receptors in complex with competitive antagonists hampers the understanding of orthosteric inhibition, hindering the further design and optimization of those antagonists for drug discovery. We determined the cryogenic electron microscopy (cryo-EM) structures of the mammalian P2X7 receptor in complex with two classical competitive antagonists of pyridoxal-5'-phosphate derivatives, pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4',8'-disulfonate) (PPNDS) and pyridoxal phosphate-6-azophenyl-2',5'-disulfonic acid (PPADS), and performed structure-based mutational analysis by patch-clamp recording as well as molecular dynamics (MD) simulations. Our structures revealed the orthosteric site for PPADS/PPNDS, and structural comparison with the previously reported apo- and ATP-bound structures showed how PPADS/PPNDS binding inhibits the conformational changes associated with channel activation. In addition, structure-based mutational analysis identified key residues involved in the PPNDS sensitivity of P2X1 and P2X3, which are known to have higher affinity for PPADS/PPNDS than other P2X subtypes. #1: ![]() Title: Structural insights into the orthosteric inhibition of P2X receptors by non-ATP-analog antagonists Authors: Sheng D / Yue C / Jin F / Wang Y / Ichikawa M / Yu Y / Guo CR / Hattori M | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 32.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.2 KB 15.2 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.6 KB | Display | ![]() |
Images | ![]() | 26.7 KB | ||
Filedesc metadata | ![]() | 5.6 KB | ||
Others | ![]() ![]() | 59.5 MB 59.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8jv7MC ![]() 8jv8C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Map
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Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_36670_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_36670_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : P2X7 trimer
Entire | Name: P2X7 trimer |
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Components |
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-Supramolecule #1: P2X7 trimer
Supramolecule | Name: P2X7 trimer / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: P2X purinoceptor
Macromolecule | Name: P2X purinoceptor / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 38.716234 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GSSTNYGTIK WIFHALVFSY ISFALISDKR YQKKEPLISS VHTKVKGIAE VKAEILENGM KKMVSGVFDT ADYTFPLQGN SFFVMTNFI KTEGQQQGLC PDFPTARTIC SSDRGCKKGR MDPQSKGIQT GRCVVYKERL KTCEVSAWCP IEEVKDAPRP A LLNSAENF ...String: GSSTNYGTIK WIFHALVFSY ISFALISDKR YQKKEPLISS VHTKVKGIAE VKAEILENGM KKMVSGVFDT ADYTFPLQGN SFFVMTNFI KTEGQQQGLC PDFPTARTIC SSDRGCKKGR MDPQSKGIQT GRCVVYKERL KTCEVSAWCP IEEVKDAPRP A LLNSAENF TVLIKNNIDF PGHNYTTRNI LPGVNITCTF HKTQNPQCPI FRLGDIFQET GDSFSDVAIQ GGIMGIEIYW DC NLDGWFH HCRPKYSFRR LDDKTTSESL YPGYNFRYAK YYKENNVEKR TLIKVFGIRF DILVFGTGGK FNVIQLAVYI GSV ISYFGL ATVFIDILIN TYSASS UniProtKB: P2X purinoceptor |
-Macromolecule #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 6 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #3: 4-[(E)-[4-methanoyl-6-methyl-5-oxidanyl-3-(phosphonooxymethyl)pyr...
Macromolecule | Name: 4-[(E)-[4-methanoyl-6-methyl-5-oxidanyl-3-(phosphonooxymethyl)pyridin-2-yl]diazenyl]benzene-1,3-disulfonic acid type: ligand / ID: 3 / Number of copies: 3 / Formula: UO6 |
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Molecular weight | Theoretical: 511.378 Da |
Chemical component information | ![]() ChemComp-UO6: |
-Macromolecule #4: water
Macromolecule | Name: water / type: ligand / ID: 4 / Number of copies: 3 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.3 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |